Antimicrobials 1 -Smith Flashcards
describe the characteristics of gram (+) cells and antibiotics?
-have a cell wall composed of thick peptidoglycan layer which this is the target of many antimicrobials
describe the characteristics of gram (-) cells and antibiotics?
- have a thin peptidoglycan cell wall and they have an LPS cell membrane outside
- the penicillin binding proteins are hard to target with antimicrobials b/c of the cell membrane
what the the structure of B lactam antimicrobials?
double ring
how do B lactam antimicrobials work?
- they resemble D- Alanine end of the peptide that serves as a substrate for transaminopeptidase enzymes
- essentially B-lactam’s are inserted into the cell wall
the be effective B lactam’s must be what 4 things?
- evade bacterial defenses
- penetrate outer cell layers to inner cytoplasmic membrane
- keeps it’s B lactam ring intact
- bind to transpeptidase (penicillin binding protein- PBP)
what do gram (+) organisms have outside the cell wall that can inactivate penicillin?
penicillinases (B lactamases)
what are transpeptidase enzymes and what is their function?
-they crosslink adjacent glycan chains by removing the terminal D-alanine residue
how B lactams
B-lactams bind to the active site of penicillin binding protein and prevent transpeptidation. The bacteria than can not make new peptidoglycan autolyses.
B-lactam drugs are only effective on what type of organisms?
-they are inactive against?
- rapidly dividing organisms
- inactive against: fungi, viruses, mycobacteria (organisms without a peptidoglycan later)
what are the 5 types of B lactam antimicrobials?
- natural penicillins
- aminopenicillins = “extended spectrum penicillins”
- Penicullinase-resistant penicillins = “antistaphylococcal penicullin)
- Anti pseudomonal penicillins
- Cephalosporins
what are the types of Natural Penicillins?
- Penicillin G
2. Penicillin VK
What is the mechanism of Natural penicillins
- Inhibits transpeptidase (penicillin-binding protein)
- Activates autolytic enzymes
are Natural penicillins bacteriostatic or bacteriocidal?
bacteriocidal
effect of penicillinase onNatural penicillins ?
-they are sensitive to penicillinase (B lactamases)
Natural Penicillins are used to clinically treat what?
Streptococci, penumococci, enterococci (w aminoglycosides) miningococci, treponema palladium
Natural Penicillins are effective against what type of organisms?
gram + cocci and less on gram (-) except nisseria species
Toxicity of Natural Penicillins?
hypersensativity reactions
-hemolytic anemia
what are the penicillinase-resistant penicillins?
- methicillin
- Nafcillin
- oxacillin
- dicloxacillin
what is the mechanism of penicillinase-resistant penicillins?
- Inhibits transpeptidase (penicillin-binding protein)
- Activates autolytic enzymes
- bacteriocidal
what are the 3 Beta-lactamase inhibitors?
- clavulanate
- sublactam
- tazobactam
what is unasyn?
ampicillin + sublactam
what is the spectrum of penicillin?
narrow spectrum
non MRSA Staphylococcal infections are treated with what?
-Naficillin - “Naf for Staph” - this is a penicillinase resistant penicillin
What are examples of Aminopenicillins?
- ampicillin
- axomicillin
mechanism of Aminopenicillins?
- Inhibits transpeptidase (penicillin-binding protein)
- Activates autolytic enzymes
- bacteriocidal
spectrum of Aminopenicillins?
-wide spectrum when combined with clavulanic acid
effect of B lactamase on Aminopenicillins ?
penicillinase sensitive - paired w clavulanic acid to inhibit this effects
what type of organisms are Aminopenicillins effective against?
gram + bacteria and gram (-) rods
what is the drug of choice for prophylaxis of infective endocarditis?
amoxicillin (Aminopenicillin) or cephalexin if allergic
what is the drug of choice for Listeria monocytogenes and enterococci?
Aminopenicillins
what is a toxicity risk of Aminopenicillins?
pseudomembranous colitis
how does probenecid effect the clearance of Ampicillin?
probenecid slows renal excretion of Ampicillin
what is the mnemonic for Ampicillin?
‘AMPing up AMO HELPS kill a wide spectrum of enterococci’
what can inactivate ampicillin when mixed in IV solutions?
hydrocortisone
what are the Anti-pseudomonal Penicillins
Anti-pseudomonal Penicillins -Ticarcillin -Carbenicillin -Piperacillin TCP: Takes Care of Pseudomonas
mechanism of Anti-pseudomonal Penicillins and spectrum of activity?
- Inhibits transpeptidase (penicillin-binding protein)
- Activates autolytic enzymes
- bacteriocidal
- extended spectrum
is Anti-pseudomonal Penicillins sensitive to penciillinase?
-yes penicillinase sensitive
Anti-pseudomonal Penicillins are used to treat what?
pseudomonas and gram (-) rods
-synergistic with aminoglycosides
what is the broadest spectrum penicillin?
piperacillin
how are cephalosporins excreted?
renally excreted
what are the 1st generation cephalosporins?
Cefazolin (IV), Cephalexin
oral
what do the 1st generation cephalosporins treat?
When are they typically used?
Mnemonic:
-Gram (+): also some Gram (-) Proteus mirabilis E. coli Klebsiella pneumonia -typically used before surgery Mnemonic: 1st Generation for a PEcK
what are the second generation cephalosporins?
Cefoxitin
Cefaclor
Cefuroxime
what do the second generation cephalosporins treat?
2nd Gnereration for a HEN PEcK —gram (-)
- Haemophilus Influenza
- Enterobacter aerogenes
- Neisseria
- Proteus mirabilis
- E. coli
- Klebsiella pneumonia
how does penicillinase effect cephalosporins?
cephalosporins = penicillinase resistant
what are the 3rd generation cephalosporins?
Ceftriaxone,
Cefotaxime,
Ceftazidime,
cefdinir
what do the 3rd generation cephalosporin’s treat?
that type of organisms?
mnemonic?
3rd Generation crosses BBB
-Gram positive and gram-negative cocci and gram
negative bacilli,
-treats :Meningitis, anaerobes, and gonococci, pseudomonas
-Mnemonic: Tri to TAX TAZ! (3rd Generation). Third generation individual drugs Pseudomonas (ceftazidine), anaerobes (ceftozoxime), and gonococci (ceftriaxone)
What are examples of 4th generation cephalosporins?
Cefepime
What do 4th generation cephalosporins treat?
4th Generation Pseudomonas
what are examples of 5th generation cephalosporins?
ceftaroline
what can 5th generation cephalosporins be used to treat?
MRSA
toxicity risk of cephalosporins
- hypersensitivity rxns to increasing toxicity of aminoglycosides
- pseudomembranous colitis
what is the mechanism of Aztreonam?
- Inhibits transpeptidase (penicillin-binding protein)
- Activates autolytic enzymes
- bacteriocidal
are Aztreonam Penicillins sensitive to penciillinase?
B lactamase resistant
Aztreonam is effective against what type of organisms?
gram negative aerobic rods
Mnemonic: Aztreonam treats a SPiKe
-Serratia, Pseudomonas, klebsiella
what is the risk of toxicity of Aztreonam?
pseudomonas colitis - overgrowth of C. difficile
when should Aztreonam be used?
Use with ‘penicillin-allergic’ patients and those with renal
insufficiency who cannot tolerate
what can be done to increase the coverage of Aztreonam?
pair it with Vancomycin or clindamycin
what are the carbapenems?
- imipenem
- meropenem
- ertapenem
what is the mechanism of carbapenems?
- Inhibits transpeptidase (penicillin-binding protien)
- Activates autolytic enzymes
- bacteriocidal
are carbapenems sensitive to penicillinase?
-penicillinase resistant ( b lackam resistant)
what is the drug of choice for enterobacteria?
Carbapenems
What is the risk of toxicity for carbapenems?
CNS toxicity
Imipenem (carbapenem) must be paired with _______ and why?
imipenum must be paired with cilistatin (an inhibitor of renal dihydropeptidase1) to decrease inactivation in renal tubules
how are carbapenems excreted?
renally excreted
what is the broadest antibacterial available?
imipenum + cilistatin
carbapenems are effective against what type of organisms?
gram positive cocci
gram negative rods
anaerobes
mechanism of vancomycin?
Inhibits cell wall formation by binding D-ala, D- ala portions of cell wall precursors
what is vancomycin used to treat?
treats multidrug resistant gram (+): Staphylococcus aureus and Clostridium difficile
what is the risk of toxicity of vancomycin?
Nephrotoxicity, Ototoxicity, Thrombophlebitis, Flushing ‘red man syndrome’
Mnemonic: The Red Man will NOT take Vanco
what is the mechanism of Bacitracin?
Blocks peptidoglycan synthesis
what is the risk of toxicity of Bacitracin?
Nephrotoxicity Ototoxicity
what is the mechanism of Daptomycin
Inserts into cell membrane, forming ion channels that disrupt ionic concentration gradient of bacteria (BACTERICIDAL)
Daptomycin is used to treat what?
Vancomycin- and methicillin-resistant Gram (+) bacteria
how does amoxicillin effect methotrexate?
amoxicillin dose dependently inhibits renal tubular secretion of methotrexate = high serum levels
how is ampicillin administered?
parenterally (IV)
Aminopenicillins treat what bugs?
H. influenza, enterics like E. coli, Salmonella, Shigella
what are the anti staphylococcal penicillins?
Methicillin, nafcillin, oxacillin, dicloxacillin
what happens as the generation of cephalosporins goes from 1 to 5?
the gram positive activity decreases and it becomes more resistant to B-lactamase enzymes
what type of cephalosporins do superinfections occur in and why?
–more likely in 2nd, 3rd, and 4th generation cephalosporins b/c they have reduced gram positive activity (particularly against enterococci)
what is the first drug of choice for surgical prophylaxis?
cefazolin - a 1st generation cephalosporin
are Cephalosporins penacillinase resistant??
yes Cephalosporins are resistant to penicillinase enzymes
B lactamase resistant antibiotics?
- penicillinase resistant penicillins( methicillin, nafacillin…etc
- cephalosporins
- azetreonam
- carbapenems
